Oncogenes are a group of genes which, when activated, can cause cancer. Most normal cells undergo a programmed form of death (apoptosis); activated oncogenes can cause those cells that ought to die to survive and proliferate instead. Most oncogenes require an additional step, such as mutations in another gene or exposure to environmental factors, to cause cancer. One method of oncogenesis occurs by the process of translocation, in which a segment of the chromosome breaks off and attaches to another chromosome. If the dislocated chromosome contains an oncogene, it may be removed from its usual regulatory controls and be continuously produced, thereby destabilizing the delicate balance of the mechanisms of cell growth. Many leukemias and lymphomas are caused by translocations of oncogenes. Since the 1970s, dozens of oncogenes have been identified in human cancer.
MYC is an oncogene overexpressed in 30% of all human cancers, and in many cancers it correlates with poor clinical outcome and increased chance of relapse [1]. c-Myc links growth factor stimulation and cell proliferation [2, 3]. Mitogenic growth factor signaling induces MYC expression. c-Myc, a basic helix-loop-helix leucine zipper transcription factor, forms heterodimers with Max to positively regulate transcription of proliferation-associated genes which include genes involved in metabolism, protein synthesis and cell-cycle [2, 3]. Thus, growth factor signaling promotes cell proliferation through inducing c-Myc's function in regulating transcription of proliferation-associated genes.
Myc is an attractive target for cancer therapy, as it is overexpressed in many human cancers that are difficult to treat and its expression is limited to proliferating cells. Studies in transgenic mouse models suggest that inactivation of MYC causes tumor regression through tumor cell differentiation or apoptosis [15-20]. In some models, such as the mouse osteosarcoma model, brief MYC inactivation significantly improved survival rates [19]. It has been suggested that the brief inactivation might induce an epigenetic change in the tumor cells such that reactivation would not necessarily cause tumor reformation. These studies also revealed that a wide variety of tumors depend on c-Myc function to maintain their tumorigenic state [15-20].
In most cancers, MYC overexpression correlates with poor clinical outcome, aggressiveness and advanced stage of cancer [1, 21]. Additionally, MYC overexpression correlates with an increased proliferative capacity. Importantly, MYC overexpression correlates with lack of response to chemotherapy and increases the probability of relapse in many cancers [1]. Developing therapies targeting the c-Myc regulatory pathway would greatly improve the therapeutic options for these aggressive, refractory malignancies.